Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

Young-Il Kim, Kwang-Min Yu, June-Young Koh, Eun-Ha Kim, Se-Mi Kim, Eun Ji Kim, Mark Anthony B. Casel, Rare Rollon, Seung-Gyu Jang, Min-Suk Song, Su-Jin Park, Hye Won Jeong, Eung-Gook Kim, Ok-Jun Lee, Yong-Dae Kim, Younho Choi, Shin-Ae Lee, Youn Jung Choi, Su-Hyung Park, Jae U. Jung () and Young Ki Choi ()
Additional contact information
Young-Il Kim: Chungbuk National University
Kwang-Min Yu: Chungbuk National University
June-Young Koh: Korea Advanced Institute of Science and Technology (KAIST)
Eun-Ha Kim: Chungbuk National University
Se-Mi Kim: Chungbuk National University
Eun Ji Kim: Chungbuk National University
Mark Anthony B. Casel: Chungbuk National University
Rare Rollon: Chungbuk National University
Seung-Gyu Jang: Chungbuk National University
Min-Suk Song: Chungbuk National University
Su-Jin Park: Gyeongsang National University
Hye Won Jeong: Chungbuk National University
Eung-Gook Kim: Chungbuk National University
Ok-Jun Lee: Chungbuk National University
Yong-Dae Kim: Chungbuk National University
Younho Choi: Lerner Research Institute, Cleveland Clinic
Shin-Ae Lee: Lerner Research Institute, Cleveland Clinic
Youn Jung Choi: Lerner Research Institute, Cleveland Clinic
Su-Hyung Park: Korea Advanced Institute of Science and Technology (KAIST)
Jae U. Jung: Lerner Research Institute, Cleveland Clinic
Young Ki Choi: Chungbuk National University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1–2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

Date: 2022
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DOI: 10.1038/s41467-021-27717-3

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